Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Mapping Genome Occupancy in Embryonic Stem Cells
Data
Global Transcriptional Repression by PRC2
Key Developmental Regulators Are Targets of PRC2
PRC2 and Highly Conserved Elements
Signaling Genes Are Among PRC2 Targets
Activation of PRC2 Target Genes During Differentiation
Supplementary Information
Acknowledgements
References
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PRC2 and Highly Conserved Elements
Previous studies have noted that many highly conserved non-coding elements of
vertebrate genomes are associated with genes encoding developmental
regulators (Bejerano et al., 2004; Siepel et al., 2005; Woolfe et al., 2005). Given
Suz12's strong association with this class of genes, we investigated the
possibility that Suz12 bound regions are associated with these highly conserved
elements. Inspection of individual genes suggested that Suz12 occupancy was
associated with regions of sequence conservation (Figure 5A). Eight percent of
the approximately 1,400 highly conserved non-coding DNA elements described
by Woolfe and colleagues (Woolfe et al., 2005) were found to be associated with
the Suz12-bound developmental regulators (p-value 10-14). Using entries from
the PhastCons database of conserved elements (Siepel et al., 2005), we found
that Suz12 occupancy of highly conserved elements was highly significant (using
highly conserved elements with a LoD conservation score of 100 or better, the pvalue
for significances was less than 10-85). Since PRC2 has not been shown to
directly bind DNA sequences, we expect that specific DNA-binding proteins
occupy the highly conserved DNA sequences and may associate with PRC2,
which spreads and occupies adjacent chromatin. Thus, the peaks of Suz12
occupancy might not be expected to precisely colocate with the highly conserved
elements, even if these elements are associated with PRC2 recruitment. Remarkably, the degree of the association between Suz12 binding and
conserved sequences increases when considering sequences with an increasing
degree of conservation (Figure 5B). By comparison, RNA polymerase II showed
no such enrichment. These results suggest that the subset of highly conserved
non-coding elements at genes encoding developmental regulators may be
associated with PcG mediated silencing of these regulators.
Suz12 binding is associated with highly conserved regions - Figure 5.
Developmental transcription factors bound by Suz12 (Table S11).
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